RENAL CONTROL OF ACID-BASE BALANCE

Physiology III, Tri IV

Guyton & Hall, Chapter 30, page 392
Dr. Robyn Strader

I. Kidneys
A. secrete acidic or basic urine
B. large amounts of bicarbonate ions are filtered by tubules
C. large amounts of H+ are filtered by tubules
D. body produces 80 mEq of nonvolatile acids/day from protein metabolism
nonvolatile acids = are not H2CO3,  not excreted by the lungs
E. the primary method for removal of body acid is renal excretion
F. kidney prevent loss of bicarbonate (more important than excretion of acids)
G. body filters 4320 mEq of bicarbonate/day (180  24 mEq/liter)
H. almost all bicarbonate is reabsorbed from the tubules
I. 4320 mEq of H+ must be secreted each day to reabsorb the filtered bicarbonate
J. an additional 80 milliequivalents must be secreted to rid the body of nonvolatile acids
(4320 + 80 = 4400 mEq of H+ secreted into the tubular fluid each day)
K. H+   reabsorption of bicarb   bicarbonate excretion
alkalosis   bicarb excretion   [H+] in extracellular
L. in acidoses, the kidney reabsorb all the filtered bicarbonate and produce new
bicarbonate
M. Kidneys regulate extracellular fluid hydrogen ion concentration by:
1. secretion of hydrogen ions
2. reabsorption of filtered bicarbonate ions
3. production of new bicarbonate ions
 100

80

[H+] 60
(nEq/L)
40

20

0
7.0 7.2 7.4 7.6 7.8 8.0
pH
II. Secretion of H+ and reabsorption of bicarbonate ions by the renal tubule
A. H+ secretion & HCO3 reabsorption occur in almost all parts of the tubules except the

descending and ascending thin limbs of the loop of Henle (see figure 30-4)
B. for a HCO3 to be absorbed, there must be a H+ secreted
C. 80 - 90% of H+ secretion and HCO3 reabsorption occurs in the proximal tubule
D. 10% in thick ascending limb
E. remaining amount is reabsorbed in distal tubule and collecting duct
F. in the Proximal tubule, H+ is counter transported with Na+ (see figure 30-5)
** G. for every H+ secreted into the tubular lumen, a bicarbonate ion enters the blood
H. HCO3 does not diffuse into renal tubular cells very well
1. it must first bind with H+ to form H2CO3
2. it then becomes CO2 and H2O
3. CO2 diffuses into cell and binds with H2O under the influence of carbonic
anhydrase to form H2CO3
4. H2CO3 dissociates to form HCO3 and H+
I. each time a H+ is formed in the tubular epithelial cells, a HCO3 is also formed and
released back into the blood
J. in the distal tubule and collecting duct, (5%) H+ are actively secreted by the
intercalated cells
1. the dissolved CO2 in the cell combines with H2O to form H2CO3
2. the H2CO3 then dissociated into HCO3 (goes to blood) and H+ (secreted into
tubule via ATP-ase pump)
 3. H+ moves via ATPase pump in distal tubule and collecting duct and counter-
transport in proximal tubule

K. in the proximal tubule [H+] can be increased 3-4 fold, even though large amounts of
H+ are present
L. in the distal tubule, [H+] can be increased as much as 900-fold
M. this lowers urine pH to about 4.5

Interstitium Lumen
Na + HCO3
Na Na
ATP
K H
HCO3 + H

H2CO3 H2CO3
carbonic
anhydrase
H2O
+
CO2 CO2 CO2 + H2O

III. Excess H+, phosphate and ammonia buffers

A. only a small amount of excess hydrogen ions can be excreted in the urine in the
form of H+
B. minimal urine pH is 4.5 = [H+] of 10-45 mEq/L or 0.03 mEq/Liter
C. for each liter of urine formed, a maximum of 0.03 mEq of free H+ can be excreted
D. therefore, to excrete the 80 mEq of nonvolatile acid formed each day would require

2667 liters of urine

E. ammonia and phosphate buffers are used to remove the excess H+
 Interstitium Lumen
Cl
Cl
ATP
H
HCO3 + H

H2CO3
carbonic
anhydrase
H2O
+
CO2 CO2

Interstitium Lumen
Na + NaHPO4
Na Na
ATP
K H
HCO3 + H

H2CO3 H + NaHPO4
carbonic
anhydrase
H2O
+
CO2 CO2 NaH2PO4

Interstitium Lumen

Glutamine Glutamine Glutamine

Cl

2HCO3 2NH4
NH4 NH4 + Cl
Na Na

IV. Phosphate Buffer system

 A. composed of HPO4= and H2PO4-
1. both become concentrated in the tubular fluid
2. both are poorly reabsorbed
B. pK of phosphate system is 6.8
C. in the urine, phosphate buffer system normally functions near its most effective range
D. after H+ binds with HPO4= to form H2PO4-, it can be excreted as a sodium salt
(NaH2PO4)
E. under normal conditions, much of the phosphate is reabsorbed and is not available for
buffering H+
F. much of the H+ buffering system is due to ammonia

Interstitium Lumen
NH3 NH3
Na Na
ATP
K H Cl
HCO3 + H

H2CO3
carbonic NH4 + Cl
anhydrase
H2O
+
CO2 CO2

V. Ammonia Buffering System

A. composed of NH3 (ammonium) and NH4+ (ammonia ion)
B. NH4+ is synthesized from glutamine
C. glutamine:
1. transported into the epithelial cells of proximal tubule, thick ascending limb
of the loop of Henle and distal tubules
2. is metabolized to form two NH4+ and HCO3
 D. NH4+ is secreted into the tubular lumen by the counter-transport mechanism in

exchange for sodium, which is reabsorbed

E. HCO3- moves with Na+ into interstitial fluid and into capillaries
F. for each molecule of glutamine metabolized in the proximal tubules,
two NH4+ ions are secreted into the urine and two HCO3- ions are reabsorbed
into the blood
G. the HCO3- formed constitutes new bicarbonate
H. in the collecting duct:
1. H+ is secreted by the tubular membrane into the lumen
2. combines with NH3 to form NH4+ which is then excreted
3. the collecting ducts are permeable to NH3 , it can easily diffuse into
tubular lumen
4. luminal membrane in collecting ducts is less permeable to NH4+
5. Once H+ has reacted with NH3 to form NH4, it is trapped in the tubular
lumen and eliminated in the urine
6. for each NH4+ excreted, a new HCO3- is generated and added
to the blood
I. increase ECF H+ concentration stimulates renal glutamine metabolism and
increases the formation of NH4+ and new bicarbonate to the be used in H+
buffering
J. a decrease in [H+] has the opposite effect
K. Under normal conditions, the amount of H+ eliminated by the ammonia buffer
system accounts for about 50% of the acid excreted and 50% of the new
bicarbonate generated by the kidneys
L. during chronic acidosis, the dominant mechanism by which acid is eliminated
and bicarbonate is generated is excretion of NH4+

VI. Quantifying Renal Acid-Base Excretion

 A. bicarbonate excretion = urine flow rate X urinary bicarbonate concentration
B. indicates how rapidly the kidneys are removing bicarbonate ions from the
blood ( = adding H+ to the blood)
C. bicarbonate added to the blood = H+ secreted with non-bicarbonate urinary
buffers (urine flow rate X urinary NH4+ concentration)

VII. Regulation of Renal Tubular Hydrogen Ion Secretion

A. H+ secretion by the tubular epithelium is necessary for:
1. bicarbonate reabsorption
2. generation of new bicarbonate associated with titratable acid formation
B. H+ secretion must be carefully regulated if the kidney are to regulated acid-
base homeostasis
C. under normal conditions:
1. the kidney tubules must secrete at least enough H+ to reabsorb almost
all the bicarbonate that is filtered
2. there must be enough H+ left over to be excreted as titratable acid or
NH4+ to rid the body of the nonvolatile acids produced each day from
metabolism
D. in alkalosis:
1. tubular secretion of H+ must be reduced to a level that is too low to
achieve complete bicarbonate reabsorption - enabling the kidneys to
increase bicarbonate excretion
2. titratable acid and ammonia are not excreted because there are no
excess H+
available to combine with non-bicarbonate buffers
3.  there is no new bicarbonate added to the urine in alkalosis

E. in acidosis:
1. tubular H+ secretion must be increased sufficiently to reabsorb all the
filtered bicarbonate and-
2. have enough H+ left over to excrete large amounts of NH4 and
 titratable acid
3. large amounts of new bicarbonate ions are added to the blood
F. the most important stimuli for H+ secretion by the tubules in acidosis are:
1. an increase in Pco2 of the extracellular fluid
2. an increase in H+ of the extracellular fluid (pH)
G. aldosterone stimulates the secretion of H+ by the intercalated cells of the
collecting duct (Conn's syndrome)  excessive secretion of H+ and
increased bicarbonate added back to the blood  alkalosis
H. in alkalosis:
1. H+ secretion
2. can occur as a result of a decreased extracellular Pco2
3. can occur as a result of a H+ concentration

pH H+nEq/L Pco2 mm Hg HCO3 mEq/L

Normal 7.4 40 40 24
Respiratory Acidosis    
Respiratory Alkalosis    
Metabolic Acidosis    
Metabolic Alkalosis    

VIII. Renal Correction of Acidosis

A. acidosis occurs when ratio of HCO3- to CO2 in the extracellular fluid
decreases  pH
B. if the ratio decreases due to fall in HCO3- = metabolic acidosis
C. if pH falls due to Pco2 = respiratory acidosis
D. in acidosis:
1. kidneys reabsorb all the filtered bicarbonate
2. kidneys contribute new bicarbonate through the formation of NH4+ and
titratable acid
E. metabolic acidosis = H+/HCO3- in tubule fluid due to filtration of HCO3
 F. respiratory acidosis = H+ in tubular fluid due to rise in extracellular fluid
Pco2, which stimulates H+ secretion
G. with chronic acidosis there is NH4+ production

IX. Renal Correction of Alkalosis

A. alkalosis = ratio of HCO3- to CO2 in the extracellular fluid , causing
a rise in pH
B. excess bicarbonate ions in tubules are excreted in the urine

X. Clinical Causes of Acid-Base Disorders

RESPIRATORY ACIDOSIS
A.  pulmonary ventilation   Pco2  H2CO3 &  H+  respiratory acidosis
B. causes of respiratory acidosis:
1. damaged respiratory center
2. decreased ability of lungs to eliminate CO2
3. obstruction of respiratory tract passageways
4. pneumonia
5.  pulmonary membrane surface area
6. interference with gas exchange
C. respiratory acidosis compensatory responses:
1. buffers of the body fluids
2. kidneys

RESPIRATORY ALKALOSIS
A. caused by overventilation by the lungs
B. generally not caused by physical pathological conditions - but psychoneurosis
C. high altitude - low O2 stimulates respiration  CO2 and mild respiratory
alkalosis

METABOLIC ACIDOSIS
 A. caused by  extracellular fluid bicarbonate concentration
B. metabolic acidosis = all other types of acidosis besides those caused by excess
CO2 in the body fluid
C. causes of metabolic acidosis
1. failure of the kidneys to excrete metabolic acids normally formed in
the body
2. formation of excess quantities of metabolic acids in the body
3. addition of metabolic acids to the body by ingestion of infusion
of acids
4. loss of base from the body fluids, which has the same effect as adding
an acid to the body fluids
5. other causes:
a. renal tubular acidosis
b. diarrhea
c. vomiting
d. diabetes mellitus
e. ingestion of acids
f. chronic renal failure

METABOLIC ALKALOSIS
A. caused by increased extracellular fluid bicarbonate concentrations
B. retention of bicarbonate of loss of H+
C. not as common as acidosis
D. causes:
1. administration of diuretics
2. excess aldosterone
3. vomiting of gastric contents
4. ingestion of alkaline drugs
(FIG. 30-10)

Arterial Blood Sample

 pH

Acidosis Alkalosis

Metabolic Respiratory Metabolic Respiratory

Respiratory Renal Respiratory Renal

Compensation Compensation Compensation Compensation